アデノウイルス媒介のヘム酸化酵素-1遺伝子発現は,血管の滑らかな筋肉細胞におけるアポプトシスを刺激する
Xiao-ming Liu1, Gary B Chapman, Hong Wang
1Houston VA Medical Center and the Department of Medicine, Baylor College of Medicine, Houston, Tex 77030, USA.
Circulation
|January 5, 2002
まとめ
血管の滑らかな筋肉細胞における血中酸素酶-1 (HO-1) の過剰発現はアポプトシスを誘発し,血管疾患に対する遺伝子治療を示唆する. ビリヴェルディンとビリルビンはまた,細胞死を促進しますが,COと鉄はそうではありません.
科学分野:
- 血管生物学 血管生物学
- セルラー・シグナリング
- 遺伝子療法の遺伝子治療法
背景:
- ヘム酸化酵素-1 (HO-1) は,血管の滑らかな筋肉細胞 (SMC) で誘導されるが,その特定の役割は不明である.
- HO-1はヘムをビリヴェルディン,鉄,一酸化炭素 (CO) に代謝する.
研究 の 目的:
- ネズミの大動脈SMCにおけるHO-1の生物学的役割を調査する.
- SMCの増殖とアポトーシスに対するHO-1過剰発現の影響を決定する.
主な方法:
- 再結合アデノウイルス (AdHO-1) を使用したラット大動脈SMCにおけるHO-1の過剰発現.
- HO-1発現,SMC増殖,アポトーシスマーカー (DNA断片化,アネキシンV,カスパース-3) およびp53レベルの評価.
- SMCにビリヴェルジン,ビリルビン,CO,または鉄を投与する.
主要な成果:
- AdHO-1感染は,HO-1の発現を増加させ,SMCの増殖を投与量に依存した方法で抑制しました.
- HO-1過剰発現は,著しくSMCアポトシスを刺激し,DNAの断片化,アネキシンVのラベル付け,カスパース3の活性化,およびp53発現の増加によって証明されました.
- 外因性ビリヴェルディンとビリルビンはSMCアポトシスを促進したが,COと鉄はそうしなかった.
結論:
- HO-1,ビリヴェルディン,またはビリルビンの過剰発現は,血管の滑らかな筋肉細胞におけるアポトーシスを誘発する.
- アデノウイルス媒介のHO-1遺伝子転送は,閉塞性血管疾患の潜在的な治療戦略を示しています.
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